4NST
Crystal structure of human Cdk12/Cyclin K in complex with ADP-aluminum fluoride
Summary for 4NST
| Entry DOI | 10.2210/pdb4nst/pdb |
| Descriptor | Cyclin-dependent kinase 12, Cyclin-K, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total) |
| Functional Keywords | transcription, rna polymerase ii, phosphorylation, transferase-transcription complex, transferase/transcription |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q9NYV4 O75909 |
| Total number of polymer chains | 4 |
| Total formula weight | 145829.09 |
| Authors | Boesken, C.A.,Farnung, L.,Anand, K.,Geyer, M. (deposition date: 2013-11-29, release date: 2014-03-26, Last modification date: 2024-10-16) |
| Primary citation | Bosken, C.A.,Farnung, L.,Hintermair, C.,Merzel Schachter, M.,Vogel-Bachmayr, K.,Blazek, D.,Anand, K.,Fisher, R.P.,Eick, D.,Geyer, M. The structure and substrate specificity of human Cdk12/Cyclin K. Nat Commun, 5:3505-3505, 2014 Cited by PubMed Abstract: Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases. PubMed: 24662513DOI: 10.1038/ncomms4505 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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